Purcell L J, Mottram P L
Department of Surgery, Royal Melbourne Hospital, Parkville, Australia.
Transplant Proc. 1995 Jun;27(3):2166-7.
In the NOD/Lt recipient mice, disease recurrence in untreated isografts was extremely rapid (median less than 10 days) compared to the rejection of an untreated BALB/c pancreas graft in a CBA mouse (median 26 days). This would be expected since disease recurrence is a secondary response in diabetic mice with lymphocytes primed to respond to the beta-cell autoantigen. The median survival time for the untreated CBA to NOD/Lt pancreas graft falls, as expected, between these two survival times (median 20 days). Although anti-CD4 and/or anti-CD8 were effective in delaying or stopping autoimmune disease recurrence and rejection in the separate models, they were unsuccessful in significantly altering survival times in the combined model, despite using 2-mg doses and dual therapy. Similar doses of anti-CD4 have failed to prevent islet allograft rejection in NOD/Lt mice. Long-term dual treatment may be required to inactivate CD4+ and CD8+ T cells in the NOD/Lt mouse to prevent both autoimmune disease recurrence and rejection. NOD/Lt recipients will require greater immunosuppression to prevent rejection-autoimmune disease recurrence will be easier to prevent. This study shows the value of using NOD/Lt mice, with naturally occurring type 1 diabetes, for assessment of immunosuppressive therapy to prevent failure of pancreas transplants.
在NOD/Lt受体小鼠中，未处理的同基因移植的疾病复发极其迅速（中位时间少于10天），这与CBA小鼠中未处理的BALB/c胰腺移植的排斥反应（中位时间26天）相比。这是可以预料的，因为疾病复发是淋巴细胞已被致敏以对β细胞自身抗原作出反应的糖尿病小鼠中的二次反应。未处理的CBA到NOD/Lt胰腺移植的中位生存时间如预期的那样，介于这两个生存时间之间（中位时间20天）。尽管抗CD4和/或抗CD8在单独的模型中有效地延迟或阻止了自身免疫性疾病的复发和排斥反应，但在联合模型中，尽管使用了2毫克剂量和联合疗法，它们在显著改变生存时间方面并不成功。类似剂量的抗CD4未能预防NOD/Lt小鼠的胰岛同种异体移植排斥反应。可能需要长期联合治疗来使NOD/Lt小鼠中的CD4+和CD8+T细胞失活，以预防自身免疫性疾病的复发和排斥反应。NOD/Lt受体将需要更大程度的免疫抑制来预防排斥反应——自身免疫性疾病的复发将更容易预防。这项研究显示了使用患有自然发生的1型糖尿病的NOD/Lt小鼠来评估免疫抑制疗法以预防胰腺移植失败的价值。
